scholarly journals Inter-Species Differences in the Response of Sinus Node Cellular Pacemaking to Changes of Extracellular Calcium

2019 ◽  
Author(s):  
Axel Loewe ◽  
Yannick Lutz ◽  
Norbert Nagy ◽  
Alan Fabbri ◽  
Christoph Schweda ◽  
...  
Keyword(s):  
Computational Models ◽  
Calcium Concentration ◽  
Species Differences ◽  
Sinus Node ◽  
Small Animal ◽  
High Rate ◽  
Human Model ◽  
Ion Concentrations ◽  
Intracellular Ion Concentrations ◽  
Small Animal Models

AbstractChanges of serum and extracellular ion concentrations occur regularly in patients with chronic kidney disease (CKD). Recently, hypocalcemia, i.e. a decrease of the extra-cellular calcium concentration [Ca2+]o, has been suggested as potential pathomechanism contributing to the unexplained high rate of sudden cardiac death (SCD) in CKD patients. In particular, there is a hypothesis that hypocalcaemia could slow down natural pacemaking in the human sinus node to fatal degrees. Here, we address the question whether there are inter-species differences in the response of cellular sinus node pacemaking to changes of [Ca2+]o. Towards this end, we employ computational models of mouse, rabbit and human sinus node cells. The Fabbri et al. human model was updated to consider changes of intracellular ion concentrations. We identified crucial inter-species differences in the response of cellular pacemaking in the sinus node to changes of [Ca2+]o with little changes of cycle length in mouse and rabbit models (<83 ms) in contrast to a pronounced bradycardic effect in the human model (up to > 1000 ms). Our results suggest that experiments with human sinus node cells are required to investigate the potential mechanism of hypocalcaemia-induced bradycardic SCD in CKD patients and small animal models are not well suited.

scholarly journals Intracellular ion concentrations and cation-dependent remodelling of bacterial MreB assemblies

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dávid Szatmári ◽  
Péter Sárkány ◽  
Béla Kocsis ◽  
Tamás Nagy ◽  
Attila Miseta ◽  
...  
Keyword(s):  
Ionic Strength ◽  
Calcium Concentration ◽  
Ion Concentration ◽  
Filtration Method ◽  
E Coli ◽  
Ion Concentrations ◽  
Rickettsia Rickettsii ◽  
Gram Positive Bacteria ◽  
Polymer Formation ◽  
Intracellular Ion Concentrations

Abstract Here, we measured the concentrations of several ions in cultivated Gram-negative and Gram-positive bacteria, and analyzed their effects on polymer formation by the actin homologue MreB. We measured potassium, sodium, chloride, calcium and magnesium ion concentrations in Leptospira interrogans, Bacillus subtilis and Escherichia coli. Intracellular ionic strength contributed from these ions varied within the 130–273 mM range. The intracellular sodium ion concentration range was between 122 and 296 mM and the potassium ion concentration range was 5 and 38 mM. However, the levels were significantly influenced by extracellular ion levels. L. interrogans, Rickettsia rickettsii and E. coli MreBs were heterologously expressed and purified from E. coli using a novel filtration method to prepare MreB polymers. The structures and stability of Alexa-488 labeled MreB polymers, under varying ionic strength conditions, were investigated by confocal microscopy and MreB polymerization rates were assessed by measuring light scattering. MreB polymerization was fastest in the presence of monovalent cations in the 200–300 mM range. MreB filaments showed high stability in this concentration range and formed large assemblies of tape-like bundles that transformed to extensive sheets at higher ionic strengths. Changing the calcium concentration from 0.2 to 0 mM and then to 2 mM initialized rapid remodelling of MreB polymers.

scholarly journals Rationally repurposed nitroxoline inhibits preclinical models of Epstein–Barr virus-associated lymphoproliferation

2021 ◽  
Author(s):  
Maite Ibáñez de Garayo ◽  
Wendi Liu ◽  
Nicole C. Rondeau ◽  
Christopher B. Damoci ◽  
JJ L. Miranda
Keyword(s):  
Epstein Barr Virus ◽  
Small Animal ◽  
Preclinical Models ◽  
Bet Inhibitor ◽  
Barr Virus ◽  
Chelating Activity ◽  
Metal Chelating ◽  
Small Animal Models ◽  
Epstein Barr ◽  
Tract Infections

AbstractRepurposing of currently used drugs for new indications benefits from known experience with those agents. Rational repurposing can be achieved when newly uncovered molecular activities are leveraged against diseases that utilize those mechanisms. Nitroxoline is an antibiotic with metal-chelating activity used to treat urinary tract infections. This small molecule also inhibits the function of bromodomain and extraterminal (BET) proteins that regulate oncogene expression in cancer. Lymphoproliferation driven by the Epstein–Barr virus (EBV) depends on these same proteins. We therefore tested the efficacy of nitroxoline against cell culture and small animal models of EBV-associated lymphoproliferation. Nitroxoline indeed reduces cell and tumor growth. Nitroxoline also acts faster than the prototype BET inhibitor JQ1. We suggest that this rational repurposing may hold translational promise.

scholarly journals History of IgA Nephropathy Mouse Models

2021 ◽  
Vol 10 (14) ◽  
pp. 3142
Author(s):  
Batoul Wehbi ◽  
Virginie Pascal ◽  
Lina Zawil ◽  
Michel Cogné ◽  
Jean-Claude Aldigier
Keyword(s):  
Iga Nephropathy ◽  
Small Animal ◽  
Experimental Models ◽  
Murine Models ◽  
Therapeutic Approaches ◽  
Complement Components ◽  
Simple Description ◽  
Primary Glomerulonephritis ◽  
History Of ◽  
Small Animal Models

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

X-ray microanalysis of intracellular ions in the anaerobic halophilic eubacterium Haloanaerobium praevalens

1997 ◽  
Vol 43 (6) ◽  
pp. 588-592 ◽  
Author(s):  
Aharon Oren ◽  
Mikal Heldal ◽  
Svein Norland
Keyword(s):  
Electron Microscope ◽  
High Variability ◽  
Sodium Potassium ◽  
X Ray ◽  
Ion Concentrations ◽  
Major Cation ◽  
Transmission Electron ◽  
Intracellular Ion Concentrations ◽  
Intracellular Ions ◽  
Chloride Concentrations

The intracellular concentrations of Na+, K+, and Cl− of the anaerobic halophilic eubacterium Haloanaerobium praevalens were assayed by means of X-ray microanalysis with the transmission electron microscope. Apparent intracellular cation concentrations between 1.22 and 1.91 M and chloride concentrations of 0.93–1.57 M were measured in cells growing exponentially in 2.6 M total salts. In exponentially growing cells, K+ was the major cation (70% of the cation sum). Stationary phase cells showed a high variability among individual cells, some of the cells containing higher Na+ than K+ concentrations.Key words: Haloanaerobium praevalens, intracellular ion concentrations, sodium, potassium, X-ray microanalysis.

Abstract 228: Alterations of Cardiac Morphology and Function Caused by Cardio-Thoracic Surgery in Small Animal Models of Heart Disease

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Peter Nordbeck ◽  
Leoni Bönhof ◽  
Karl-Heinz Hiller ◽  
Sabine Voll ◽  
Paula Arias ◽  
...  
Keyword(s):  
Body Weight ◽  
Heart Disease ◽  
Animal Models ◽  
Right Ventricular ◽  
Small Animal ◽  
Cardiac Morphology ◽  
Small Animal Models ◽  
And Function

Background: Surgical procedures in small animal models of heart disease, such as artificial ligation of the coronary arteries for experimental myocardial infarction, can evoke alterations in cardiac morphology and function. Such alterations might induce artificial early or long term effects in vivo that might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies in small animal models of heart disease. Methods: Female Wistar rats were matched for weight and distributed to sham left coronary artery ligation or untreated control. Cardiac parameters were then investigated in vivo by high-field MRI over time after the surgical procedure, determining left and right ventricular morphology and function. Additionally, the time course of several metabolic and inflammatory blood parameters was determined. Results: Rats after sham surgery showed a lower body weight for up to 8 weeks after the intervention compared to healthy controls. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in the sham operated rats compared to the controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed prolonged metabolic and inflammatory changes after surgery not related to cardiac disease. Conclusion: There is a small distinct impact of cardio-thoracic surgical procedures on the global integrity of the organism, which in the long term also includes circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective studies and transferring the findings to conditions in patients.

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